The p53 family, including p53, p63, and p73, play pivotal roles in various biological functions and are vitally relevant to cancer biology. Autophagy is an evolutionarily conserved catabolic process and stress-response mechanism that is activated by diverse cellular stressors. It performs distinct roles at different stages of cancer, spanning carcinogenesis, progression, and therapy response. Multiple studies have shed light on how p53 modulates autophagy and the underlying mechanisms involved, but some studies also show the involvement of p63 and p73 in autophagy. It is important to note that the localization of p53 in the cytoplasm or the nucleus, has distinct effects on autophagy regulation. Cytoplasmic and basal p53 generally suppress autophagy, whereas nuclear or activated p53 usually promotes autophagy through transcription-dependent and independent mechanisms. In contrast, mutant p53 commonly acts as a negative regulator of autophagy. Remarkably, activated TA isoforms of p63 and p73, distinguished by their complete transactivation domain function compared to the ΔN isoforms, can stimulate autophagy through both transcription-dependent and independent mechanisms. This enhances our comprehension of p53 family involvement in autophagy regulation. Additionally, a plethora of anticancer drugs have been pinpointed as autophagy inducers, functioning through the modulation of the p53 family signaling cascade. In this review, we look at the mechanisms by which the p53 family modulates autophagy, providing insights into novel strategies for cancer therapy by the manipulation of the p53 family/autophagy signaling cascade.
Hsin et al. (Tue,) studied this question.